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Silensomes

A Smart Choice for Human Cytochromes P450 Phenotyping Assays

 

Available now!…Silensomes™

Drug-drug interaction can significantly impact drug safety and efficacy. Prediction of this risk of drug-drug interactions is a requisite in the development of a new drug candidate and the submission of the registration dossier. In vitro identification and measurement of the contribution of the major cytochrome P450 enzymes involved in the human metabolism of a new drug candidate, also called “CYP phenotyping”, helps predict the impact of co-administered drug(s), or perpetrator(s), on the pharmacokinetics of the new chemical entity, or the victim. Up until now, these studies are carried out using three common approaches: correlation analysis, antibody or chemical inhibition, and metabolism by recombinant human enzymes. These tests have a number of disadvantages.

Models such as correlation analysis provide no direct quantitative measurement of the contribution of each CYP in the metabolism of a drug, including:

  • Models such as recombinant CYP450 enzymes are not fully representative of the liver enzyme profile
  • Many chemical and antibody inhibitors lack sufficient specificity to enable confidence in results

To overcome the disadvantages of the current methodologies, a patented new in vitro drug development model was developed.

Introducing Silensomes™

Silensomes™ are validated human pooled liver microsomes (HLMs) chemically and irreversibly inactivated for one specific CYP using mechanism based inhibitors (MBI).

Each Silensomes™ is available as cryopreserved, ready-to-use HLMs chemically knocked-out for one specific CYP activity (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4) with each showing high specificity and efficiency of their targeted CYP inhibition (>80%), and only minor impact (<20%),

The thaw and go format of Silensomes™ enables researchers to focus more on results and less on validating the level of CYP inhibitions.  Silensomes™ are available now from Lonza for compound screening purposes and for regulatory validation.

Case Study: CYP3A4-Silensomes™

CYP3A4 activity is specifically and extensively inhibited in CYP3A4-Silensomes™

CYP3A4-Silensomes™ and its homologous control were incubated with different CYPspecific substrates.

Results showed:

  • CYP3A4 mediated metabolism of testosterone, a pure CYP3A4substrate, was totally inhibited.
  • More than 80% of CYP3A4-mediated metabolism of nifedipine and midazolam was inhibited. Residual metabolism of these substrates was inhibited by ketoconazole, revealing the CYP3A5 contribution.
  • There was no impact on the other CYP activities tested.


Silensomes™

Catalogue Number Description
SIL200 Human hepatic CYP3A4-Silensomes™
SIL210 Human hepatic CYP1A2-Silensomes™
SIL220 Human hepatic CYP2A6-Silensomes™
SIL230 Human hepatic CYP2B6 Silensomes™
SIL240 Human hepatic CYP2D6-Silensomes™
SIL250 Human hepatic CYP2C8-Silensomes™
SIL260 Human hepatic CYP2C9-Silensomes™
SIL270* Human hepatic CYP2C19-Silensomes™
SIL280* Human hepatic CYP2E1-Silensomes™

Control Silensomes™

Catalogue Number Description
SIL201 Human hepatic Control CYP3A4-Silensomes™
SIL211 Human hepatic Control CYP1A2-Silensomes™
SIL221 Human hepatic Control CYP2A6-Silensomes™
SIL231 Human hepatic Control CYP2B6 Silensomes™
SIL241 Human hepatic Control CYP2D6-Silensomes™
SIL251 Human hepatic Control CYP2C8-Silensomes™
SIL261 Human hepatic Control CYP2C9-Silensomes™
SIL271* Human hepatic CYP2C19-Silensomes™
SIL281* Human hepatic Control CYP2E1-Silensomes™

*Coming soon.

To order Silensomes, contact Customer Service at (800)638-8174 or customerservice-trl@lonza.com.

We offer great discounts on bulk orders of cryopreserved hepatocytes. Contact us for more information.